PHYSIOLOGY, ENDOCRINOLOGY, AND REPRODUCTION Influence of Aminoguanidine, an Inhibitor of Inducible Nitric Oxide Synthase, on the Pulmonary Hypertensive Response to Microparticle Injections in Broilers1

ABSTRACT The pulmonary hypertensive response to pulmonary vascular obstruction caused by intravenously injected microparticles is amplified by pretreatment with Nωnitro-L-arginine methyl ester (L-NAME). The L-NAME prevents the synthesis of the potent vasodilator nitric oxide (NO) by inhibiting both the constitutive [endothe-lial NO synthase (eNOS or NOS-3)] and inducible [induc-ibleNO synthase (iNOSorNOS-2)] forms ofNOsynthase. In the present study we used the selective iNOS inhibitor aminoguanidine (AG) to evaluate the role of iNOS in modulating the pulmonary hypertension (PH) triggered by microparticle injections. Experiment 1 was conducted to confirm the ability of AG to inhibit NO synthesis by iNOS in broiler peripheral blood mononuclear cells ex-posed to bacterial lipopolysaccharide (LPS, endotoxin). Mononuclear leukocytes treated with LPS produced 10-fold more NO than untreated (control) cells. The LPS-stimulated production of NO was partially inhibited by L-NAME andwas fully inhibited by AG, thereby confirm-ing that AG inhibits LPS-mediated iNOS activation in broilers. In Experiment 2 we evaluated the responses of male progeny from a base population (MP Base) and from a derivative line selected for one generation from the Key words: nitric oxide, aminoguanidine, pulmonary hypertensio